This invention relates to penicillin and cephalosporin antibiotics. In particular it relates to 6-substituted-6-acylamidopenicillanic acids, 7-substituted-7-acylamidocephalosporanic acids, 7-substituted-7-acylamidodeacetoxycephalosporanic acids, the esters and pharmaceutically acceptable salts of the foregoing acids, and to a process and intermediates useful in the preparation thereof.
Heretofore many semi-synthetic penicillins and cephalosporin antibiotics have been prepared by the acylation of 6-aminopenicillanic acid (6-APA), 7-aminocephalosporanic acid (7-ACA) and 7-aminodeacetoxycephalosporanic acid (7-ADCA) with a wide variety of acyl groups. In addition, many novel cephalosporin antibiotics have been synthesized by substitution reactions involving the methylene group in the 3-position of the dihydrothiazene ring of the cephalosporin nucleus. However, the literature contains scant information on penicillins and cephalosporin antibiotics having a substituent attached to one of the carbon atoms of the .beta.-lactam ring.
Since the prediction by J. L. Strominger and D. J. Tipper, Amer. J. Med. 39, 708 (1965), that 6-methyl penicillins and 7-methyl cephalosporins should have enhanced microbiological activity and the recent discovery of the 7-methoxycephalosporins obtained from the fermentation of Streptomycete organisms by R. Nagarajan, et al., J. Amer. Chem. Soc., 93, 2308 (1971), considerable interest has developed in the synthesis of .beta.-lactam antibiotics having a substituent .alpha. to the .beta.-lactam carbonyl of the penicillin and cephalosporin antibiotics.